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Article Dans Une Revue Frontiers in Immunology Année : 2023

Loss of NOD2 in macrophages improves colitis and tumorigenesis in a lysozyme-dependent manner

Camille Chauvin
  • Fonction : Auteur
Katarina Radulovic
  • Fonction : Auteur
Olivier Boulard
  • Fonction : Auteur
Myriam Delacre
  • Fonction : Auteur
Nadine Waldschmitt
  • Fonction : Auteur
Paul Régnier
  • Fonction : Auteur
Gauthier Legris
  • Fonction : Auteur
Clément Bouchez
  • Fonction : Auteur
Mohamed-Yassine Sleimi
  • Fonction : Auteur
Philip Rosenstiel
  • Fonction : Auteur
Guillaume Darrasse-Jèze
  • Fonction : Auteur
Mathias Chamaillard
  • Fonction : Auteur

Résumé

Background Crohn’s disease (CD) is a complex and poorly understood myeloid-mediated disorder. Genetic variants with loss of function in the NOD2 gene confer an increased susceptibility to ileal CD. While Nod2 in myeloid cells may confer protection against T-cell mediated ileopathy, it remains unclear whether it may promote resolution of the inflamed colon. In this study, we evaluated the function of Nod2 in myeloid cells in a model of acute colitis and colitis-associated colon cancer (CAC). Methods To ablate Nod2 specifically within the myeloid compartment, we generated LysM Cre/+ ;Nod2 fl/fl mice. The role of NOD2 was studied in a setting of Dextran Sodium Sulfate (DSS)-induced colitis and in azoxymethane (AOM)/DSS model. Clinical parameters were quantified by colonoscopy, histological, flow cytometry, and qRT-PCR analysis. Results Upon DSS colitis model, LysM Cre/+ ;Nod2 fl/fl mice lost less weight than control littermates and had less severe damage to the colonic epithelium. In the AOM/DSS model, endoscopic monitoring of tumor progression revealed a lowered number of adenomas within the colon of LysM Cre/+ ;Nod2 fl/fl mice, associated with less expression of Tgfb . Mechanistically, lysozyme M was required for the improved disease severity in mice with a defect of NOD2 in myeloid cells. Conclusion Our results indicate that loss of Nod2 signaling in myeloid cells aids in the tissue repair of the inflamed large intestine through lysozyme secretion by myeloid cells. These results may pave the way to design new therapeutics to limit the inflammatory and tumorigenic functions of NOD2.

Dates et versions

hal-04276983 , version 1 (09-11-2023)

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Citer

Camille Chauvin, Katarina Radulovic, Olivier Boulard, Myriam Delacre, Nadine Waldschmitt, et al.. Loss of NOD2 in macrophages improves colitis and tumorigenesis in a lysozyme-dependent manner. Frontiers in Immunology, 2023, 14, ⟨10.3389/fimmu.2023.1252979⟩. ⟨hal-04276983⟩

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